Faculty of Humanities; School of Human and Community development; MA Research Report / Social participation is one of the most debilitating effects of aphasia. Yet, to date no clear definitions or models of social participation have been developed that can be applied within aphasiology. In addition, generic stroke scales are still the outcome measures of choice within research. There is a need for patient-centred measures that accurately document and assess the experiences and perceptions of those with aphasia. Therefore, the current research aimed to investigate the social participation of adults with aphasia by extending patient-centred measures and encompassing the views of the families, particularly the spouses, of those with aphasia. Four crosssectional parallel single case studies were conducted that involved a protocol combining the quantitative measure of the ASHA FACS with the qualitative tools of semi-structured interviews and observations. In addition, social network analyses were completed for each participant. Overall, open coding of the individual participants’ results produced common themes among the people with aphasia and common themes among their spouses. Each participant reported significantly altered social participation, which permeated throughout the family unit and was felt considerably by the spouses of those with aphasia. The results are discussed in relation to current social models and approaches to intervention, while professional role expansion and the needs of the South African context are also considered. Furthermore, the concept of resilience and its implications for future research are discussed.

Lors de la liaison d’un glucocorticoïde (GC) naturel ou synthétique (par exemple, la Dexaméthasone) au récepteur des glucocorticoïdes (GR), les GCs régulent l’expression de gènes cibles soit par (i) transactivation par liaison ‘’directe’’ à un élément de liaison à l’ADN de type ‘’(+)GRE’’, (ii) transrépression ‘’directe’’ par liaison à un élément de type ‘’nGRE’’ ou (iii) transrépression ‘’indirecte’’ par interaction physique directe avec des facteurs de transcription pro-inflammatoires tels que AP-1 et NF-κB. Les effets anti-inflammatoires bénéfiques des GCs sont généralement attribués à la transrépression indirecte, alors que nombre de leurs effets secondaires pathologiques indésirables paraissent liés à la transactivation et/ou à la transrépression directe. Notre laboratoire a récemment découvert qu’un composé non-stéroïdien dénommé CpdX ainsi que ses dérivés deutérés, ne présentent ni la fonction de transactivation, ni celle de transrépression directe du GR, tout en stimulant son activité bénéfique de transrépression indirecte. Notre projet a consisté à caractériser un composé non-stéroïdien dit CpdX, ainsi que ses dérivés, quant à leurs activités thérapeutiques et à démontrer qu’elles sont semblables à celles des glucocorticoïdes anti-inflammatoires, couramment utilisés, tout en étant débarrassés de leurs effets pathologiques secondaires, tels que l’ostéoporose, l’atrophie cutanée et le syndrome métabolique. Pour atteindre nos objectifs, nous avons utilisés des modèles de souris présentant soit les affections cutanées (dermatites de contact ou atopique, psoriasis), l'asthme, l’arthrite rhumatismale, la colite ulcérative ou la conjonctivite allergique, associés à des études d’immunologie et de biologie moléculaire et cellulaire. Mon travail de thèse a démontré que CpdX, et certains de ses dérivés deutérés, présentent une activité anti-inflammatoire dans le traitement de ces modèles ‘’souris’’ (Partie I). Nous avons aussi montré que le traitement par CpdX et ses dérivés n’induit pas les effets secondaires pathologiques des glucocorticoïdes (Partie II), ouvrait ainsi la vue à une nouvelle ère dans le traitement à long-terme de maladies inflammatoires, sans provoquer les effets pathologiques indésirables des traitements actuels aux glucocorticoïdes. / Upon binding of natural or synthetic glucocorticoids (GCs) (e.g. Dexamethasone) to their glucocorticoid receptor (GR), GCs regulate the expression of target genes either by (i) direct transactivation through direct binding to “(+)GRE” DNA binding sites (DBS), (ii) direct transrepression through binding to “IR nGRE” DBSs or (iii) tethered indirect transrepression mediated through interaction with transactivators, such as NFkB, AP1, or STAT3 bound to their cognate DBSs. The beneficial anti-inflammatory effects of GCs have been generally ascribed to tethered transrepression, whereas many of their long-term undesirable side-effects could be due to transactivation and/or direct transrepression. Our laboratory recently reported that a non-steroidal compound, named CpdX, selectively lacks both direct transactivation and direct transrepression functions, while still exerting an indirect transrepression activity. The goal of our project was to characterize CpdX and some of its derivatives as effective anti-inflammatory drugs similar to glucocorticoids, but lacking their main deleterious side-effects, e.g. osteoporosis, skin atrophy and metabolic disorders. To this end, we have used experimental mouse model for skin disorders (atopic dermatitis, contact dermatitis, and psoriasis), asthma, rheumatoid arthritis, ulcerative colitis and allergic conjunctivitis, combined with immunology, molecular and cellular biology. My thesis studies have demonstrated that in mouse models, CpdX and its derivatives exhibit anti-inflammatory activities, which are similar to those of glucocorticoids (Part I). Importantly, we further show that CpdX and its derivatives do not exhibit the long-term debilitating side-effects of glucocorticoids (Part II). Thereby paving the way to a new era in the long-term therapy of major inflammatory diseases.

Rheumatoid Arthritis (RA) is a disease in which the body has "turned on itself", with its immune system attacking mobility. In RA, an immune mechanism attacks and destroys the joints and limits mobility, in some circumstances to the point of needing replacement of joints. The aim of this research is the development of a less costly, widely accessible, passive sensing technology that provides a quantitative assessment of RA and that monitors the therapeutic effectiveness on joint-debilitating diseases. The proposed solution relies on a quantitative evaluation of human gestures. Such a quantitative assessment supports the comparison between the motion capabilities of a patient and that of a healthy person, using a kinematic model of the human skeleton. Criteria for the classification of severity were established, and tables were generated to classify the levels of severity as a function of the measurements extracted from processed videos of a subject performing predefined movements. This research project, while contributing a new tool to the process of classification of RA level of severity, opens the way for using widely accessible digital imaging for diagnosing and monitoring the evolution of the illness. Replacing MRI or HRUS with a cheaper and more accessible technology would have a major impact on health care services. From the clinical point of view, the proposed techniques based on digital images processing combined with a monitoring approach based on infrared images that was previously developed may provide a utility of care for patients with RA, as well as an alternative and automated approach for early detection of RA and active inflammation at a critical time.

Rheumatoid Arthritis (RA) is a disease in which the body has "turned on itself", with its immune system attacking mobility. In RA, an immune mechanism attacks and destroys the joints and limits mobility, in some circumstances to the point of needing replacement of joints. The aim of this research is the development of a less costly, widely accessible, passive sensing technology that provides a quantitative assessment of RA and that monitors the therapeutic effectiveness on joint-debilitating diseases. The proposed solution relies on a quantitative evaluation of human gestures. Such a quantitative assessment supports the comparison between the motion capabilities of a patient and that of a healthy person, using a kinematic model of the human skeleton. Criteria for the classification of severity were established, and tables were generated to classify the levels of severity as a function of the measurements extracted from processed videos of a subject performing predefined movements. This research project, while contributing a new tool to the process of classification of RA level of severity, opens the way for using widely accessible digital imaging for diagnosing and monitoring the evolution of the illness. Replacing MRI or HRUS with a cheaper and more accessible technology would have a major impact on health care services. From the clinical point of view, the proposed techniques based on digital images processing combined with a monitoring approach based on infrared images that was previously developed may provide a utility of care for patients with RA, as well as an alternative and automated approach for early detection of RA and active inflammation at a critical time.